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Biomedical subjects

M Page

Publications and source records attributed to M Page.

At least 91 records · Page 5Linked to original sources
PubMed1991

Studies on the immunogenicity of Chinese hamster ovary cell-derived recombinant gp120 (HIV-1IIIB).

Recombinant DNA-derived gp120 (HIV-1IIIB) expressed in chinese hamster ovary cells elicited specific humoral and cell-mediated immune responses in a variety of mammals. Antisera from immunized rabbits, sheep and goats recognized virus-derived gp120 and its precursor (gp160). Neutralizing antibodies were also elicited, but only in a few animals, and this may be related to the protein's susceptibility to cleavage through the neutralizing domain. However, in rabbits the degree of cleavage of gp120 had little or no effect on its antigenicity or immunogenicity. All antisera had limited cross-reactivity to envelope glycoproteins from a panel of HIV-1 isolates suggesting that immunodominant antibody epitopes are in variable regions of the recombinant gp120. Antigen-specific T-cell responses were detected in immunized macaques and were found to be stronger and more prolonged when gp120 was administered in Freund's adjuvant rather than alum.

Animals↗
PubMed1991

Caregiving and multigenerational families.

This paper examines the possibility that the extension of traditional family household boundaries foreshadows an expanded caregiving system as family lines grow longer. An original study of 25 four-generation families, mapping all linear and lateral members, offers findings that confirm evidence found in a literature review. One primary caregiver, either a spouse or daughter, generally shoulders responsibility for members in adversity. A caregiving system encompassing more than two generations in direct descent was not discernible. Problems in caring for the oldest old are noted.

Adolescent↗
PubMed1991

Antisera raised against recombinant soluble CD4s can have reactivity to recombinant HIV-1 envelope glycoproteins.

Antisera from sheep immunized with two different recombinant soluble CD4 preparations both exhibited cross-reactive antibodies specific for recombinant gp120s and gp160s prepared in different expression systems in immunoblots and radiobinding assays. The cross-reactivity was broadly mapped to the amino-terminal 70K cleavage fragment of gp120 and more closely identified to residues 204-274 using a series of truncated recombinant gp120s. However, this reactivity could not be detected against virally encoded gp160/120.

Animals↗
PubMed1990

The production and purification of PCR-derived recombinant simian immunodeficiency virus p27 gag protein; its use in detecting serological and T-cell responses in macaques.

The polymerase chain reaction (PCR) was used to amplify a region of the gag gene, encompassing the core protein p27, from genomic DNA of cells infected with SIVmac251 (32H isolate). The 767 base pair PCR product was cloned into the bacteriophage M13 and fully sequenced before sub-cloning into the expression vector pUC19. The 30 kilodalton (kDa) fusion protein of lacZ-p27 was expressed as a soluble protein in E. coli JM101 cells and purified to greater than 90% purity by affinity chromatography. The affinity purified product was used in serological and T-cell assays to assess immune function in cynomolgus macaques immunised or challenged with immunodeficiency virus derived material. This reagent and accompanying methods provide valuable assays for monitoring the efficacy of vaccines for SIV as a model for human AIDS.

Animals↗
PubMed1990

The ocular effects of intracarotid bromodeoxyuridine and radiation therapy in the treatment of malignant glioma.

Since July 1985, 23 patients have been entered into a phase I/II clinical trial using intraarterial 5-bromodeoxyuridine (BUdR) (400-600 mg/m2 daily for 8.5 weeks) and focal external beam radiotherapy (59.4 Gy at 1.8 Gy daily in 6.5 weeks) in the treatment of malignant gliomas (Kernohan grades 3 and 4). The side effects in all patients have included varying degrees of anorexia, fatigue, ipsilateral forehead dermatitis, blepharitis, and conjunctivitis. Mucopurulent conjunctivitis and exposure keratitis developed in several patients and spontaneous corneal perforation developed in one. Eyes from two individuals examined at autopsy showed significant changes. Animal studies that predated clinical trials using rhesus monkeys did not predict the ophthalmologic complications seen in human subjects.

Adult↗
PubMed1990

Inhibition of estrogen receptor-DNA binding by the "pure" antiestrogen ICI 164,384 appears to be mediated by impaired receptor dimerization.

Many estrogen-antagonist and -agonist ligands have been synthesized, some of which have proved clinically important in the treatment of hormone-dependent breast tumors and endocrine disorders. Here we show that the "pure" antiestrogen ICI 164,384 inhibits mouse estrogen receptor-DNA binding in vitro. The effects of this steroid on DNA binding can be overcome by addition of anti-receptor antibody whose epitope lies N-terminal to the receptor DNA-binding domain. Since this antibody is also capable of restoring DNA-binding activity to receptor mutants that either lack the dimerization domain or bear deleterious mutations within it, we propose that ICI 164,384 reduces DNA binding by interfering with receptor dimerization. In contrast, when complexed with the antagonist/partial agonist tamoxifen, the estrogen receptor is capable of binding to DNA in vitro, but tamoxifen does not promote the agonist-induced conformational change obtained with estradiol. The implications of these data are discussed in relation to the in vivo properties of these drugs.

Amino Acid Sequence↗
PubMed1990

Developmental patterning of the carbohydrate antigen FC10.2 during early embryogenesis in the chick.

An oligosaccharide antigen (FC10.2), formerly described only in mammalian cells and secreted glycoproteins, has been detected and found to display striking temporal and spatial patterning in the chick during early embryonic development. This antigen is expressed on type 1 chains, which are isomers of oligosaccharides of the poly-N-acetyllactosamine series (type 2 chains). Immunoreactivities before and after neuraminidase treatment of serial sections of chick embryos during the first 17 stages of development indicate that the FC10.2 structure occurs predominantly in the sialylated form (S-FC10.2). The FC10.2 and S-FC10.2 antigens are prominent markers of the primordial germ cells, being strongly expressed by these cells from the pre-primitive streak stage onwards. S-FC10.2 is also a clear marker of the pronephric duct from its first appearance. Initially present over the entire apical surface of the ectoderm, antigenicity diminishes in an antero-posterior direction as neurulation proceeds. A unique pattern for a carbohydrate antigen is displayed by cells of the primitive streak; antigenicity is lost with de-epithelialisation and ingression, but is regained in a pericellular distribution on the mesoderm cells that emerge from the primitive streak. Thereafter, successive changes in expression and distribution of FC10.2 and S-FC10.2 are features of mesodermal tissues, particularly during somitogenesis. These antigens are prominent components of the extracellular matrix around the notochord and sclerotome cells. They are also prominent posteriorly in the subectodermal region, ceasing abruptly at the lateral limits of the embryo proper. Although no absolute correlations can yet be made, several features of the distribution of these antigens suggest that they may be integral components of, or ligands for, cell adhesion molecules.

Animals↗
PubMed1989

Early morning hyperglycemia in insulin-dependent diabetes: acute and sustained effects of cholinergic blockade.

Nocturnal release of GH has been shown to be related to the early morning rise in plasma glucose (PG) seen in insulin-dependent diabetes mellitus (IDDM). We have studied the effects of suppression of nocturnal GH release during a single night (acute study) and after nightly suppression for 1 week (chronic study). Changes in plasma glucose and counter-regulatory hormone concentrations were monitored in six IDDM patients during a constant overnight insulin infusion alone, after addition of the anticholinergic agent pirenzepine to cause acute GH suppression, and again on the seventh night of such treatment. In control experiments (infusion of insulin alone; 0.075 mU/kg.min) PG increased from (mean +/- SEM) 5.6 +/- 0.6 mmol/L at 2400 h to 11.1 +/- 1.3 mmol/L at 0900 h (P = 0.0024). Addition of pirenzepine (100 mg at 2200 h and again at 2400 h) in the acute study resulted in a PG change from 5.6 +/- 0.3 mmol/L at 2400 h to 8.4 +/- 1.4 mmol/L at 0900 h (P = 0.17). After pirenzepine administration at the same dose for 7 nights, PG increased from 4.7 +/- 0.6 mmol/L at 2400 h to 6.8 +/- 1.2 mmol/L at 0900 h (P = 0.11). Increases in PG during the study period were significantly less after chronic treatment than after acute treatment compared with changes on control nights. The nocturnal release of GH, which was demonstrated in all patients during the control nights, was suppressed in all patients during the acute study and in four of six patients during the chronic studies. We conclude that initial reduction of the early morning rise of PG in IDDM is associated with acute suppression of nocturnal GH release, and that the more significant sustained effect of anticholinergic GH suppression on the rise of PG may be associated with additional indirect effects on insulin clearance.

Adult↗
PubMed1989

Changing patterns of cytokeratins and vimentin in the early chick embryo.

The distribution of cytokeratins and vimentin intermediate filaments in the first 48 h of chick development has been determined using immunofluorescent labelling. During formation of the germ layers, cytokeratin expression is associated with the appearance of an integral epithelium (ectoderm), whereas vimentin expression is associated with cells that detach and migrate from this epithelium to form endoderm and mesoderm. Subsequently, vimentin persists in the endoderm and mesoderm and the tissues derived therefrom, such as the somites and developing heart, throughout the period of study. The appearance of cytokeratins at later stages of development occurs in some epithelia such as the ectoderm, endoderm, lateral plate and epimyocardium but not others including the neural plate, neural tube and somites. Expression of cytokeratins in endoderm and mesenchymal tissues occurs in tandem with vimentin. In conclusion, vimentin expression is related to its distribution in the epiblast before germ layer formation. Its initial appearance may be related to the motile behaviour of cells about to ingress through the primitive streak. The appearance of cytokeratin filaments, however, does not reflect germ layer derivation but rather the need for an epithelial sheet.

Animals↗
PubMed1989

Flow cytometric analysis of DNA abnormalities in colorectal carcinomas.

We report a flow cytometric study on ploidy in 117 colorectal cancers. An aneuploid cell population was found in more than 70% of adenocarcinomas. Ploidy was found to be stage-related; aneuploid tumors with DNA index greater than or equal to 1.4 were found mainly in Dukes' C and Dukes' D stages (P less than 0.02). Tumors of the caecum and of the ascending colon were more often found to be diploid than those of the other sites. There was a progressive increase in the proportion of cells in S-phase depending on whether they were from normal tissue, inflammatory mucosa or adenocarcinomas. The proportion of cells in S-phase was significantly larger in aneuploid tumors (P less than 0.001). The data presented above suggest that aneuploidy and the proportion of non-resting cells could be important prognostic factors for colorectal cancers. The latter are independent of the stage of the disease and histological differentiation.

Adenocarcinoma↗
PubMed1988

Ambiguous effect of chlorpromazine on doxorubicin activity against P388D1 tumours in mice.

Chlorpromazine (CPZ) can decrease the toxicity of doxorubicin (DOX). We wanted to determine whether this CPZ pretreatment could affect the response of tumours to therapeutic doses of DOX. Six groups of eight female CDF1 mice received 1 million leukaemia P388D1 cells i.p. For 5 days, they received DOX i.p. (total dose 0, 6 or 12 mg/kg), preceded by saline or 5 mg/kg CPZ s.c. CPZ in the absence of DOX had no effect on survival [median survival time (MST) of 19 days vs. 20]. In mice receiving DOX only, MST was greater than 60 days. Mice receiving DOX + CPZ were similar to DOX till day 25, but subsequently died earlier (MST of 27 and 34 days, for DOX 6 and 12 mg/kg). At death or day 60, 31% (5/16) of DOX mice and 88% (14/16) of DOX + CPZ had macroscopic tumours (P less than 0.005, both DOX dose groups combined). However, only 19% (3/16) of DOX and 6% (1/16) of DOX + CPZ had tumours in the abdominal cavity, the others being in the abdominal wall close to the site of injection. The results suggests that while CPZ did not affect the killing of cancer cells in the abdominal cavity, it did block the effect of DOX on cells in the abdominal wall and skin. This block may be caused by decreased local delivery of DOX, due to the hypothermia produced by CPZ.

Animals↗
PubMed1987

The effects of mechanical stability on the macromolecules of the connective tissue matrices produced during fracture healing. II. The glycosaminoglycans.

The glycosaminoglycans secreted into the matrices associated with fractures of the rabbit tibia healing under stable and unstable mechanical conditions have been characterized histochemically using the dye Alcian Blue at pH 5.7 in the presence of increasing concentrations of magnesium chloride, and after enzymatic extractions. These results are compared with those of immunohistochemical experiments using monoclonal antibodies which recognize epitopes specific to various glycosaminoglycans. The results indicate that the fibrous tissues, including those of the cavities of the cancellous bone and periosteum, possess hyaluronate and chondroitin sulphate, but the amounts present are small. The glycosaminoglycans detected in the cortical bone are located mainly around the osteocyte lacunae where chondroitin and keratan sulphates are found. The developing trabeculae of cancellous bone in the callus contain chondroitin and keratan sulphates, but as the trabeculae mature, these glycosaminoglycans are no longer present throughout the matrix; they are found particularly around the osteocyte lacunae. The cartilage in the callus of mechanically unstable fractures contains chondroitin, chondroitin-4- and 6-sulphates and keratan sulphate, through their distribution is variable. The small, transient areas of cartilage in the callus of mechanically stable fractures also contain those glycosaminoglycans, but they appear to be less highly sulphated. The mechanical stability of the fractures appears to affect the amount and degree of sulphation of the glycosaminoglycans, rather than the types of glycosaminoglycan produced. The glycosaminoglycans produced during fracture healing are compared with those produced during embryonic development and other healing processes.

Animals↗
PubMed1986

The effects of mechanical stability on the macromolecules of the connective tissue matrices produced during fracture healing. I. The collagens.

The distribution of types I, II, III, V and IX collagens in healing fractures of the rabbit tibia has been demonstrated by immunofluorescent techniques. It has also been shown that the mechanical stability of the healing fracture affects both the distribution and types of the collagens present. The initial fibrous matrix contains types III and V collagens; type I collagen was only located in this matrix if unfixed tissue was used. In mechanically stable fractures, cancellous bone forms over the entire periosteal surface by 5-7 days; type I collagen is laid down within the previous fibrous matrix. The trabeculae are heterogeneous in their collagen content. The cavities contain a matrix of types III and V collagens. Small nodules of cartilage may be present between 7 and 14 days; these contain types II and IX collagens. In mechanically unstable fractures, cancellous bone is initially formed away from the fracture gap. The fibrous tissue over the gap is replaced by cartilage; types II and IX collagens are laid down on the pre-existing fibrous matrix. The cartilage is replaced by endochondral ossification. At the ossification front, type I collagen is found around the chondrocyte lacunae of the spicules of cartilage. The new trabeculae contain a core of cartilage which is surrounded by a bone matrix of types I and V collagens. The fracture gaps are invaded by fibrous tissue, which contain types III and V collagens. this is later replaced by cancellous bone.

Animals↗